ENDEAVORING THE ROLE OF OBESITY IN EXTRACELLULAR MATRIX DEGRADATION LEADING TO METASTASIS

Abstract

One of the significant causes of death globally is cancer ( http://www.who.org/ ). Another critical problem is obesity, which is associated with an increased cancer threat. This work provides insight into how obesity contributes to cancer progression and metastasis. We developed a diffusive obesity-cancer model consisting of cancer cells, normal cells, fat cells, macrophages, and an extracellular matrix (ECM) for this aim. We have directed the formed model’s global existence and non-negativity. Equilibrium points for the related ODE are calculated, and its existence and stability study is also done. We present a traveling wave analysis of the obesity-cancer model and have calculated the minimum wave speed. Using a combination of analytic and numerical results of traveling waves, we conjecture that the minimal wave speed depends on fat cells’ diffusive rate and haptotaxis coefficient. We followed the theory of the Partial Rank Correlation Coefficient (PRCC) to carry out a global sensitivity analysis to evaluate the most sensitive parameters reliable for cancer progression. We delivered a comprehensive numerical analysis of our deterministic and diffusive models (in 1D and 2D) and analogized the result. Numerical simulation of corresponding spatially explicit systems conveys complex spatio-temporal dynamics, resulting in the appearance of patterns. It also discloses that cancer spread increases with increased haptotaxis coefficient and growth rate of obese cells. Our simulation confirms that the degradation of the ECM increases cancer spread and density.